1. Technical Field
The field of this invention is the design and fabrication of microfluidic devices.
2. Background
Microfluidic devices promise to be the method of use, where one wishes to use very small volumes for the interaction of compounds. The interaction may be to determine the binding affinity of one compound for another, the agonist or antagonist activity of one compound for an enzyme, surface membrane receptor, intracellular protein, etc., or to carry out one or more reactions. In many instances, one or more of the components will be scarce and/or expensive, so that one would wish to use the particular component efficiently. This means that one would wish to have the component in a small volume, where a substantial portion of such volume is used in the operation.
In many cases, there will be a common component in carrying out the operation. Particularly, in assaying for biological activity of candidate compounds, one may have a common protein, such as a receptor, transcription factor, enzyme, hormone, etc., a common cell, or a common competitor, where one wishes to utilize such entity efficiently and in a reproducible manner in a microfluidic device. Since in screening one would wish to screen a multitude of different compounds for different activities, desirably one would use a chip of small dimensions, where the space occupied by each of the individual units of the device is minimized or is organized to complement another device, such as a microtiter well plate. There is a substantial interest in providing microfluidic devices, which provide effective use of scarce common components and space, while permitting ready access of electrodes to wells.
Simpson, et a., Proc. Natl. Acad. Sci. 1998, 95, 22256-2261, and references cited therein, describe capillary array electrophoresis (CAE) devices. U.S. Pat. No. 5,800,690 describes methods for detecting the movement of entities in microfluidic device channels.
Microfluidic capillary array electrokinetic (CAEK) devices are provided employing individual units having four fold symmetry, each unit providing four separate subunits permitting two independent determinations, where four subunits share a single supply reservoir for a total of 8 determinations. Units share waste reservoirs, where the waste reservoirs are distributed for positioning of electrodes for electrokinetic movement of the components of an operation. Detectors may be positioned, either fixed or movable, to address each of the main or assay channels for a determination of the result of the operation. Chips are provided which allow for a 96- or 384-assay or higher assay format. The chips may be fabricated in accordance with conventional techniques and find particular application in screening candidate compounds for one or a few characteristics. Methods are provided for monitoring channel flow to provide accurate interactions and detection in the microchannels.